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Genetic Changes Tied to Common Form of Parkinson's Disease

Changes in 2 genes known to contain mutations causing rare familial
forms of Parkinson's disease have been linked with the more common,
sporadic form of the disease.

Parkinson's disease is a progressive neurologic disorder caused by
the degeneration of nerve cells in the portion of the brain that controls
movement. It affects about 1.5 million Americans. The likelihood of
developing the disorder increases with age and involves a combination
of environmental and genetic risk factors.

To better understand the genetic contributors, an international research
team embarked upon the largest genome-wide association study of Parkinson's
disease reported to date. Genome-wide association studies analyze large
amounts of DNA to identify subtle genetic variations that contribute
to disease. The researchers were led by Dr. Andrew B. Singleton of
NIH’s National Institute on Aging (NIA) and Dr. Thomas Gasser
of the University of Tubingen in Germany and the German Center for
Neurodegenerative Disease. The team was supported in part by NIA, NIH’s
National Institute of Neurological Disorders and Stroke (NINDS), National
Cancer Institute (NCI) and National Institute of Environmental Health
Sciences (NIEHS).

The researchers first analyzed DNA samples of over 1,700 Europeans
with Parkinson's disease and about 4,000 without it. In the November
15, 2009, online issue of Nature Genetics, the scientists
reported that mutations in the alpha-synuclein (SNCA) gene
and microtubule associated protein tau (MAPT) are risk factors
for sporadic Parkinson's disease. These initial findings were replicated
in a similar group of over 3,300 people with Parkinson's disease and
over 4,500 without it.

The researchers exchanged data with colleagues performing a similar
study of Japanese people. This second group also found a strong association
for SNCA, but not for MAPT. They uncovered evidence
for 2 additional risk variants that were then confirmed in the European
study. The first, named Park16, was strongest in the Japanese
population. The second variant is close to the gene LRRK2,
which Singleton and Gasser's groups had previously linked to an inherited
form of Parkinson's disease.

These findings support the idea that the sporadic and rare familial
forms of Parkinson's disease are related. "With this better understanding
of the underlying genetic variants involved in the progress of this
disorder, we have more insight into the causes and underlying biology
of this disease," says Singleton. "We hope this new understanding
will one day provide us with strategies to delay, or even prevent,
the development of Parkinson's disease."

"Future genome-wide association studies involving greater numbers
of DNA samples will likely reveal additional common genetic risk factors.
As we continue to use these and other novel approaches to understand
complex diseases, we move closer to a complete understanding of the
genetic basis of Parkinson's disease," says NIA Director Dr. Richard
J. Hodes.